How Darzalex could surge clear of its multiple myeloma rival

Darzalex’s failure in a non-Hodgkin’s lymphoma study last month was a blip for what still promises to be a major growth driver for Johnson & Johnson – at least if you believe the drug’s sellside forecasts, which have ballooned sixfold over the past two years.

Darzalex was approved for multiple myeloma in 2015 at roughly the same time as Bristol-Myers Squibb’s Empliciti; while these were then neck and neck, expectations now see Darzalex surging well clear of its rival. Novel indications – and for Darzalex there are plenty – provide only part of the reason why this might be the case (see tables below).

As such the answer might lie in Darzalex’s ability to break into front-line multiple myeloma – both drugs are being studied in this setting – and physicians’ perception of its superior efficacy. Certainly, the sellside is in no doubt which drug will win out: consensus for 2022 Empliciti sales sits at a mere $827m.

Leerink analysts recently cited a key opinion leader who said Darzalex was likely to migrate to first-line multiple myeloma. Empliciti, however, ultimately had “no role” in the relapsed/refractory setting, and would only enjoy front-line use briefly by virtue of timing.

“Over time the specialist believed Darzalex would phase out Empliciti from first and second-line use, and the [Bristol] drug seems likely to be marginalised in his practice and other centres,” Leerink wrote.

Back in 2015, of course, Empliciti was expected to bring in $836m in 2020 sales, versus Darzalex’s $551m, EvaluatePharma’s archived forecasts reveal. Darzalex’s full approval came on the back of survival in the second-line Castor and Pollux studies, and since then sellside expectations have taken off.

A first-line label is within reach of both drugs, but beyond that it will be down to novel indications, in which Darzalex is clearly ahead of Empliciti.

Selected studies of Empliciti

Indication

Study name

Combined with

Trial ID

Completion

Note

R/r multiple myeloma

Eloquent-2*

Revlimid

NCT01239797

–

Interim PFS backed approval

R/r multiple myeloma

Checkmate-602*

Opdivo & Pomalyst

NCT02726581

Nov 2018

R/r multiple myeloma

Eloquent-3

Pomalyst

NCT02654132

Sep 2017

1L multiple myeloma

Eloquent-1*

Revlimid

NCT01335399

Apr 2018

1L multiple myeloma

–

Revlimid & Velcade

NCT02375555

Oct 2018

1L multiple myeloma

–

Revlimid & Kyprolis

NCT02969837

Dec 2019

Not yet recruiting

Post-ASCT multiple myeloma maintenance

–

Revlimid

NCT02420860

Apr 2018

Smouldering multiple myeloma

–

Revlimid

NCT02279394

Jan 2020

Note: all phase II unless marked *.

Darzalex and Empliciti target different antigens seen on plasma cells – CD38 and CS1 respectively. The rationale behind Darzalex’s potential in other tumours is that CD38 is also present on immune-suppressive cells, J&J tells EP Vantage, the inhibition of which could release a brake on the immune system and allow combination with Tecentriq or Opdivo, for instance, to be effective.

However, CD38 is also present on some CD4+ and CD8+ effector T cells, so striking a balance between immune system activation and suppression could be tricky.

Either way the solid tumour indications are mere icing on the cake. Before that the battle for first-line use must be fought.

This story was amended to correct a mistake in the description of the Cassiopeia study.